Search date August 2003 Gregory Rubin QUESTIONS Effects of treatments...397 395 INTERVENTIONS CONSTIPATION Trade off between benefits and harms Cisapride with or without magnesium oxide*...397 Unknown effectiveness Biofeedback training...399 Increased dietary fibre...398 Osmotic laxatives...398 Stimulant laxatives...399 *Not widely licensed for use in children. Clinical use in adults was recently restricted because of heart rhythm abnormalities. See comments on cisapride under gastro-oesophageal reflux in children, p 455. Covered elsewhere in Clinical Evidence Constipation in adults, p 610 Key Messages Constipation Cisapride with or without magnesium oxide Two RCTs in people aged 2 18 years found that cisapride improved stool frequency and symptoms of constipation after 8 12 weeks of treatment in an outpatient setting compared with placebo. One RCT in children aged 1 7 years with chronic constipation found that combined treatment with cisapride and magnesium oxide significantly improved stool frequency after 3 4 weeks of treatment in an outpatient setting compared with magnesium oxide alone. We found no evidence from primary care settings. Use of cisapride has been restricted in some countries because of adverse cardiac effects. Biofeedback training One systematic review found no significant difference between biofeedback plus conventional treatment and conventional treatment alone in children with persisting defecation disorders at 12 months. Increased dietary fibre We found no systematic review or RCTs on the effects of increasing dietary fibre. Osmotic laxatives We found no RCTs that compared osmotic laxatives versus placebo in children. Two small RCTs found no significant difference in stool frequency or consistency between lactulose and lactitol after 2 4 weeks in children aged 8 months to 16 years. One of the RCTs found that lactulose increased abdominal pain and flatulence compared with lactitol. A third RCT in non-breastfed constipated infants found no difference between different strengths of lactulose. Stimulant laxatives One systematic review found no reliable RCTs comparing stimulant laxatives versus placebo or other treatments. Clin Evid 2004;12:395 400.
396 DEFINITION Constipation is characterised by infrequent bowel evacuations; hard, small faeces; or difficult or painful defecation. The frequency of bowel evacuation varies from person to person. 1 According to the Rome II diagnostic criteria for childhood defecation disorders, functional constipation can be defined as either having hard or pellet-like stools for the majority of stools or firm stools two or less times per week in the absence of structural, endocrine or metabolic diseases. 2 Some studies reported in this chapter used other diagnostic criteria. 3 Encopresis is defined as involuntary bowel movements in inappropriate places at least once a month for 3 months or more, in children aged 4 years and older. 4 INCIDENCE/ Constipation with or without encopresis is common in children. It PREVALENCE accounts for 3% of consultations to paediatric outpatient clinics and 25% of paediatric gastroenterology consultations in the USA. 5 Encopresis has been reported in 2% of children at school entry. The peak incidence is at 2 4 years of age. AETIOLOGY/ No cause is discovered in 90 95% of children with constipation. RISK FACTORS Low fibre intake and a family history of constipation may be associated factors. 6 Psychosocial factors are often suspected, although most children with constipation are developmentally normal. 5 Chronic constipation can lead to progressive faecal retention, distension of the rectum, and loss of sensory and motor function. Organic causes for constipation are uncommon, but include Hirschsprung s disease (1/5000 births; male to female ratio of 4 : 1; constipation invariably present from birth), cystic fibrosis, anorectal physiological abnormalities, anal fissures, constipating drugs, dehydrating metabolic conditions, and other forms of malabsorption. 5 This chapter aims to cover children in whom no underlying cause is identified. PROGNOSIS Childhood constipation can be difficult to treat and often requires prolonged support, explanation, and medical treatment. In one long term follow up study of children presenting under the age of 5 years, 50% recovered within 1 year and 65 70% recovered within 2 years; the remainder required laxatives for daily bowel movements or continued to soil for several years. 5 It is not known what proportion continue to have problems into adult life, although adults presenting with megarectum or megacolon often have a history of bowel problems from childhood. AIMS OF To remove faecal impaction and to restore a bowel habit in which INTERVENTION stools are soft and passed without discomfort; to ensure self toileting and passing stools in appropriate places. OUTCOMES METHODS Number of defecations per week; gut transit time as measured by timing the passage of radio-opaque pellets, which may be ingested within a gelatin capsule; use of laxatives; stool consistency; pain; difficulty in defecation; blood in stool; number of soilings per month. Clinical Evidence search and appraisal August 2003 using the following keywords: constipation, encopresis, diet therapy, diagnosis, therapy, psychology, stimulant laxatives, dietary fibre, and lactulose. The search was limited to infants and children. Trials were
QUESTION selected for inclusion if they focused on the management of constipation or encopresis, or both; if they were relevant to primary health care; and if they included children without an organic cause for constipation. What are the effects of treatments for constipation? CISAPRIDE 397 Two RCTs in people aged 2 18 years found that cisapride improved stool frequency and symptoms of constipation after 8 12 weeks of treatment in an outpatient setting compared with placebo. One RCT in children aged 1 7 years with chronic constipation found that combined treatment with cisapride and magnesium oxide significantly improved stool frequency after 3 4 weeks of treatment in an outpatient setting compared with magnesium oxide alone. We found no evidence from primary care settings. Use of cisapride has been restricted in some countries because of adverse cardiac effects. We found no systematic review but found three RCTs. 7 9 Versus placebo: One RCT (69 children and young adults aged 4 18 years, attending hospital with constipation, defined as pain, difficulty in defecation, or 3 4 bowel movements/week for at least 3 months in the absence of a history of bowel disease) found that cisapride 0.3 mg/kg daily (as a syrup) significantly increased stool frequency and decreased gut transit time after 8 weeks compared with placebo (mean stool frequency/week 6.75 with cisapride v 1.31 with placebo). 7 The second RCT (40 children aged 2 16 years with a history of chronic constipation referred to a paediatric hospital gastroenterology clinic) found significant benefit for cisapride compared with placebo at 12 weeks, measured by a composite of improved stool frequency, absence of faecal soiling, and no use of other laxatives (improvement in composite index 14/20 [70%] with cisapride v 7/20 [35%] with placebo; RR 2.00, 95% CI 1.03 to 3.88; NNT 3, 95% CI 1 to 24). 8 Cisapride plus magnesium oxide versus magnesium oxide alone: The third RCT (84 children aged 1 7 years, attending hospital with chronic constipation, defined as fewer than 2 spontaneous bowel movements/week for at least 1 month in the absence of any underlying medical condition or concomitant drug use) compared cisapride 0.2 mg/kg three times daily (as a syrup) plus magnesium oxide (125 mg 3 times daily for children weighing less than 20 kg and 250 mg 3 times daily for children weighing more than 20 kg) versus magnesium oxide alone. 9 Both groups showed a similar increase in stool frequency after 1 week of treatment (30/44 [68%] with cisapride plus magnesium oxide v 23/40 [58%] with magnesium oxide alone; P = 0.369). Although the number of children responding to magnesium oxide alone remained constant after 1 2 weeks of therapy, the number of those responding to the combined treatment was significantly greater after 4 weeks (40/44 [91%] with cisapride plus magnesium oxide v 27/40 [68%] with magnesium oxide alone; P = 0.013). No significant difference between the two treatment groups was found regarding stool consistency (softened in 29/44
398 [66%] children treated with cisapride plus magnesium oxide v 27/40 [68%] children treated with magnesium oxide; no change in 11 children of each treatment group; P = 0.876) or the incidence of blood in the stools (3 children in each treatment group; P = 1.0) after 4 weeks. Versus placebo: The RCTs comparing the use of cisapride versus placebo did not report harms (see comment below). 7,8 Cisapride plus magnesium oxide versus magnesium oxide alone: Adverse events reported in the RCT comparing cisapride plus magnesium oxide versus magnesium oxide alone were minimal, limited to gastrointestinal upset, and showed no significant difference between the two treatment groups (adverse effects occurred in 2 4 children [5 9%] receiving combined treatment v 1 2 children [3 5%] in the group receiving monotherapy). None of the children in the study reported any arrhythmia-related symptoms. 9 Use of cisapride has been restricted in some countries because of its association with heart rhythm abnormalities in adults. See comments on cisapride under gastro-oesophageal reflux in children, p 455. INCREASED DIETARY FIBRE We found no systematic review or RCTs on the effects of increasing dietary fibre. We found no systematic review or RCTs. We found no RCTs. None. OSMOTIC LAXATIVES We found no RCTs that compared osmotic laxatives versus placebo in children. Two small RCTs found no significant difference in stool frequency or consistency between lactulose and lactitol after 2 4 weeks in children aged 8 months to 16 years. One of the RCTs found that lactulose increased abdominal pain and flatulence compared with lactitol. A third RCT in non-breastfed constipated infants found no difference between different strengths of lactulose. Versus placebo: We found no systematic review and no placebo controlled RCTs of osmotic laxatives in children. Versus each other: We found two small RCTs 10,11 comparing the effects of lactitol versus lactulose on stool frequency and consistency and a third RCT 12 comparing the effects of two different dosages of lactulose in infants. The first RCT (51 children, aged 8 months to 16 years visiting a physician for chronic idiopathic constipation) found no significant difference in stool frequency or consistency between lactitol and lactulose at 4 weeks (stool frequency per week increased from 2.5 to 5.6 with lactitol v 2.0 to 4.8 for lactulose; significance not reported; stool consistency normal or soft in 15/23 [65%] children with lactitol v 16/19 [84%] with lactulose; reported as non-significant, no other data). 10 The second RCT (39 children,
aged 11 months to 13 years) compared lactitol 150 350 mg/kg daily versus lactulose 150 mg/kg daily over 2 weeks. 11 It found no significant difference in stool frequency between lactulose and lactitol (stool frequency in both groups was 1 1.5/day). A third RCT (220 non-breastfed, constipated infants aged 0 6 months) compared 2% and 4% lactulose mixed with an artificial milk preparation. 12 At 14 days, over 90% of parents in both groups reported easy passage of normal or thin consistency stools. However, the RCT did not compare outcomes between treatment groups. 399 Versus each other: The first RCT found that significantly fewer children taking lactitol had abdominal pain or flatulence compared with lactulose (abdominal pain: 22% with lactitol v 58% with lactulose; P < 0.005; flatulence: 30% with lactitol v 63% with lactulose; P < 0.01). 10 Versus each other: The benefits shown in the third RCT are comparisons of outcomes before and after treatment, and were not necessarily a result of the treatments. 12 STIMULANT LAXATIVES One systematic review found no reliable RCTs comparing stimulant laxatives versus placebo or other treatments. Versus placebo or alternative treatment: We found one systematic review (search date 2001), which found no RCTs of adequate methodological rigour comparing stimulant laxatives versus either placebo or alternative treatment in children (see comment below). 13 We found no subsequent placebo controlled RCTs of the effects of stimulant laxatives in children. None identified. Versus placebo or alternative treatment: The studies identified by the review were all comparative, used multiple interventions, and had small sample sizes. 13 One quasi-randomised study (using last hospital number digit to allocate patients) in 37 children (aged 3 12 years) with chronic constipation found that senna was significantly less effective in achieving daily bowel movements after 6 months than mineral oil concentrate (9/18 [50%] with senna v 16/19 [89%] with mineral oil; P < 0.05) and less effective in reducing involuntary faecal soiling after 6 months (8/18 [44%] children continuing to soil with senna v 1/19 [5%] with mineral oil; RR 8.44, 95% CI 1.52 to 16.70). 14 No significant differences were found in the number of children with at least one recurrence of constipation symptoms during the treatment period (16/18 [89%] with senna v 12/19 [66%] with mineral oil; RR 0.71, 95% CI 0.48 to 1.04). BIOFEEDBACK TRAINING One systematic review found no significant difference between biofeedback plus conventional treatment and conventional treatment alone at 12 months.
400 REFERENCES We found one systematic review (search date 2001, 8 RCTs). 3 The review found no significant difference in rates of persisting problems between conventional treatment plus biofeedback and conventional treatment alone at 12 months (OR 1.34, 95% CI 0.92 to 1.94). There was heterogeneity of borderline significance (P = 0.087). One included RCT (41 children) found a different trend from the other seven RCTs for reasons that were not apparent. 15 After exclusion of this RCT, results were no longer heterogeneous. Meta-analysis excluding this RCT found that biofeedback plus conventional treatment increased rates of persisting problems compared with conventional treatment alone (OR 1.59, 95% CI 1.07 to 2.35; heterogeneity P = 0.53). None reported. In the systematic review, sample sizes were generally small, and interventions and outcomes varied among trials. 3 1. Nelson R, Wagget J, Lennard-Jones JE, et al. Constipation and megacolon in children and adults. In: Misiewicz JJ, Pounder RE, Venables CW, eds. Diseases of the gut and pancreas. 2nd ed. Oxford: Blackwell Science, 1994;843 864. 2. Rasquin-Weber A, Hymen PE, Cucchiara S, et al. Childhood functional gastrointestinal disorders. Gut 1999;45(Suppl II):1160 1168. 3. Brazzelli M, Griffiths P. Behavioural and cognitive interventions with or without other treatments for defaecation disorders in children (Cochrane Review). In: The Cochrane Library, Issue 3, 2003. Chichester, UK: John Wiley & Sons, Ltd. Search date 2001; primary sources Cochrane Incontinence Group Trials Register, Cochrane Controlled Trials Register, hand searching of journals, and the Enuresis Resource and Information Centre Register. 4. American Psychiatric Association. Diagnostic and statistical manual of mental disorders. 4th ed. Washington, DC: American Psychiatric Association, 1994. 5. Loening-Baucke V. Chronic constipation in children. Gastroenterology 1993;105:1557 1563. 6. Roma E, Adamidis D, Nikolara R, et al. Diet and chronic constipation in children: the role of fiber. J Pediatr Gastroenterol Nutr 1999;28:169 174. 7. Halibi IM. Cisapride in the management of chronic pediatric constipation. J Pediatr Gastroenterol Nutr 1999;28:199 202. 8. Nurko MD, Garcia-Aranda JA, Worona LB, et al. Cisapride for the treatment of constipation in children: a double blind study. J Pediatr 2000;136:35 40. 9. Ni YH, Lin CC, Chang SH, et al. Use of cisapride with magnesium oxide in chronic pediatric constipation. Acta Paediatr Taiwan 2001;42:345 349. 10. Pitzalis G, Mariani P, Chiarini-Testa MR, et al. Lactitol in chronic idiopathic constipation of childhood. Pediatr Med Chir 1995;17:223 226. 11. Martino AM, Pesce F, Rosati U. The effects of lactitol in the treatment of intestinal stasis in childhood. Minerva Pediatr 1992;44:319 323. 12. Hejlp M, Kamper J, Ebbesen F, et al. Infantile constipation and allomin-lactulose. Treatment of infantile constipation in infants fed with breast milk substitutes: a controlled trial of 2% and 4% allomin-lactulose. Ugeskr Laeger 1990;152:1819 1822. 13. Price KJ, Elliott TM. What is the role of stimulant laxatives in the management of childhood constipation and soiling? In: The Cochrane Library, Issue 3, 2003. Chichester, UK: John Wiley & Sons, Ltd Search date 2001; primary sources Cochrane database of randomised controlled clinical trials, hand searching of paediatric journals, and contact with experts in the field. 14. Sondheimer JM, Gervaise EP. Lubricant versus laxative in the treatment of chronic functional constipation of children: a comparative study. J Pediatr Gastroenterol Nutr 1982;1:223 226. 15. Loening-Baucke V. Modulation of abnormal defecation dynamics by biofeedback treatment in chronically constipated children with encopresis. J Pediatr 1990;116:214 222. Gregory Rubin Professor of Primary Care University of Sunderland Sunderland UK Competing interests: None declared.